Exploiting APC function as a novel cancer therapy

Alyssa C. Lesko, Kathleen H. Goss, Jenifer Prosperi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The Adenomatous Polyposis Coli (APC) tumor suppressor is most commonly mutated in colorectal cancers such as familial adenomatous polyposis (FAP); as well as many other epithelial cancers like breast, pancreatic, and lung cancer. APC mutations usually result in a truncated form of the protein lacking the carboxy-terminal region resulting in loss of function. Mutations in APC have been identified in early stages of cancer development making it a gatekeeper of tumor progression and therefore an ideal therapeutic target. APC is best known for its role as a negative regulator of the Wnt/β -catenin pathway. However, APC also mediates several other normal cell functions independently of Wnt/β-catenin signaling such as apical-basal polarity, microtubule networks, cell cycle, DNA replication and repair, apoptosis, and cell migration. Given the vast cellular processes involving APC, the loss of these "normal" functions due to mutation can contribute to chemotherapeutic resistance. Several therapeutic treatments have been explored to restore APC function including the reintroduction of APC into mutant cells, inhibiting pathways activated by the loss of APC, and targeting APC-mutant cells for apoptosis. This review will discuss the normal functions of APC as they relate to potential treatments for patients, the role of APC loss in several types of epithelial cancers, and an overview of therapeutic options targeting both the Wnt-dependent and -independent functions of APC.

Original languageEnglish
Pages (from-to)90-102
Number of pages13
JournalCurrent Drug Targets
Volume15
Issue number1
StatePublished - 2014

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Adenomatous Polyposis Coli
Catenins
Neoplasms
Tumors
Apoptosis
Therapeutics
Repair
Cells
Mutation
DNA
Breast Neoplasms
Wnt Signaling Pathway
Proteins
DNA Replication
Pancreatic Neoplasms
Microtubules
DNA Repair
Cell Movement
Colorectal Neoplasms

Keywords

  • APC
  • Cancer
  • Targeted therapy
  • Tumor suppressor

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

Exploiting APC function as a novel cancer therapy. / Lesko, Alyssa C.; Goss, Kathleen H.; Prosperi, Jenifer.

In: Current Drug Targets, Vol. 15, No. 1, 2014, p. 90-102.

Research output: Contribution to journalArticle

Lesko, AC, Goss, KH & Prosperi, J 2014, 'Exploiting APC function as a novel cancer therapy', Current Drug Targets, vol. 15, no. 1, pp. 90-102.
Lesko, Alyssa C. ; Goss, Kathleen H. ; Prosperi, Jenifer. / Exploiting APC function as a novel cancer therapy. In: Current Drug Targets. 2014 ; Vol. 15, No. 1. pp. 90-102.
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